A dual-action niclosamide-based prodrug that targets cancer stem cells and inhibits TNBC metastasis.

ABSTRACT: Chemotherapy typically destroys the tumor mass but rarely eradicates the cancer stem cells (CSCs) that can drive metastatic recurrence. A key current challenge is finding ways to eradicate CSCs and suppress their characteristics. Here, we report a prodrug, Nic-A, created by combining a carbonic anhydrase IX (CAIX) inhibitor, acetazolamide, with a signal transducer and transcriptional activator 3 (STAT3) inhibitor, niclosamide. Nic-A was designed to target triple-negative breast cancer (TNBC) CSCs and was found to inhibit both proliferating TNBC cells and CSCs via STAT3 dysregulation and suppression of CSC-like properties. Its use leads to a decrease in aldehyde dehydrogenase 1 activity, CD44^high/CD24^low stem-like subpopulations, and tumor spheroid-formin

SUBMITTER: Kim JH 

PROVIDER: S-EPMC10214212 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature